MEGAN HITCHINS LABORATORY

Training: Ph.D in Clinical Genetics (UCL, London, UK)

Last position: Associate Professor, Stanford University

Cancer Research Focus: Translational

• Germline genetic and epigenetic risk factors in cancer predisposition (mostly high-risk setting) & inheritance

• Discovery of, and clinical testing of, DNA methylation biomarkers of cancer for the detection of circulating tumor DNA (ctDNA) for cancer screening (early diagnosis) and monitoring of cancer burden/treatment

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Research Projects Underway

Identification and clinical testing of methylated DNA biomarkers for the detection of ctDNA in plasma: Early diagnosis & monitoring for cancer progression/response to treatment

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Identification of unusual causes for cancer predisposition in high-risk groups - typically in patients/families who received negative/uninformative/limited CLIA-approved genetic test results (germline mutation, SVs, epimutation, VUS reclassification)

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Modes of intergenerational inheritance/erasure of altered constitutional epigenetic states (e.g. MLH1 “epimutation”) – which can be Mendelian and non-Mendelian

• Amend current universal screening algorithms for colorectal and endometrial cancer to routinely identify cases with “epimutation” as the cause of their mismatch repair deficiency

• Mechanistic basis: currently using linked-read WGS (Chromium/10X Genomics) to identify cis/trans SNVs, SVs, and retroelement mobilization as potential underlying mechanisms.

 

Frequently used Wet-lab Techniques

WGBS, SureSelect (deep MethylSeq), Infinium HM arrays, targeted bisulphite sequencing (NGS or clonal), ChIP, promoter reporter

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Targeted Pyrosequencing (detection & quantification of hot-spot mutations, CpG methylation, allelic expression, CNV, LOH). Applications: verification, molecular diagnostics, particularly robust for FFPE tissue samples

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Sensitive real-time PCR/droplet to detect low-levels of specific mutations, alleles, or methylation (qMSP, MethyLight, MethylHeavy). Applications: Detection of ctDNA in plasma, mosaicism